Sofosbuvir/velpatasvir

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Sofosbuvir/velpatasvir
Combination of
Sofosbuvir NS5B polymerase inhibitor
Velpatasvir NS5A inhibitor
Clinical data
Trade names Epclusa, Sofosvel, Velpanat, others
AHFS/Drugs.com Monograph
MedlinePlus a616034
License data
Pregnancy
category
Routes of
administration 		By mouth [2]
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only) [3]
  • UK: POM (Prescription only) [4]
  • US: ℞-only [5]
  • EU:Rx-only [6]
  • In general: ℞ (Prescription only)
Identifiers
CAS Number
PubChem CID
UNII
KEGG

Sofosbuvir/velpatasvir, sold under the brand name Epclusa among others, is a fixed-dose combination medication for the treatment of hepatitis C in adults. [2] [4] [5] [6] It combines sofosbuvir and velpatasvir. [2] [4] [5] It is more than 90% effective for hepatitis C genotypes one through six. [2] It also works for hepatitis C in those who also have cirrhosis or HIV/AIDS. [2] It is taken by mouth. [2] [4] [5]

Contents

In March 2020, sofosbuvir/velpatasvir was approved for use in the United States to treat hepatitis C virus (HCV) in children ages six years and older or weighing at least 37 pounds (17 kilograms) with any of the six HCV genotypes—or strains—without cirrhosis (liver disease) or with mild cirrhosis. Sofosbuvir/velpatasvir in combination with ribavirin is indicated for the treatment of children six years and older or weighing at least 37 pounds with severe cirrhosis. [7]

The combination is generally well tolerated. [2] Common side effects include headaches, fatigue, trouble sleeping, and nausea. [8] [7] The combination has not been studied in pregnant women or during breastfeeding. [8] Greater care is required in those who are also infected with hepatitis B. [8] Sofosbuvir works by blocking the NS5B protein and velpatasvir works by blocking the NS5A protein. [8]

Sofosbuvir/velpatasvir was approved for medical use in the United States and in Europe in 2016. [8] [5] [6] It is on the World Health Organization's List of Essential Medicines. [9]

Medical uses

A single tablet regimen is used for adults with genotype 1–6 chronic hepatitis C virus (HCV) infection. [5]

Contraindications

Combining sofosbuvir/velpatasvir with strong inducers of the liver enzymes CYP2B6, CYP2C8 or CYP3A4, or with P-glycoprotein, is contraindicated because such substances may reduce the effectiveness of the drug. [10]

Side effects

Common side effects (in more than 10% of people) are headache, fatigue and nausea. [8] [7] In studies, severe side effects were experienced in 3% of patients, and 0.2% terminated the therapy because of adverse events. These effects occurred with similar frequencies in people treated with placebo. [10]

Interactions

Pharmacokinetics

History

Beacon Pharmaceuticals in Bangladesh introduced a generic version product under the trade name of Sofosvel. Beacon received approval from the Directorate of Drug Administration, Ministry of Health and Family Welfare, People's Republic of Bangladesh. [11]

Sofosbuvir/velpatasvir was developed by the pharmaceutical company Gilead Sciences and approved by the U.S. Food and Drug Administration (FDA) in June 2016. [12] In the European Union it was approved in July 2016, for the treatment of chronic hepatitis C virus infection in adults. [6]

The safety and efficacy of sofosbuvir/velpatasvir for a 12-week treatment was evaluated in three Phase III clinical trials of 1,558 subjects without cirrhosis or with compensated cirrhosis (mild cirrhosis). [12] Results demonstrated that 95–99 percent of subjects who received sofosbuvir/velpatasvir had no virus detected in the blood 12 weeks after finishing treatment, suggesting the subjects' infections had been cured. [12] The safety and efficacy of sofosbuvir/velpatasvir was also evaluated in a clinical trial of 267 subjects with decompensated cirrhosis (moderate to severe cirrhosis), of whom 87 subjects received sofosbuvir/velpatasvir in combination with ribavirin for 12 weeks, and 94 percent of these subjects had no virus detected in the blood 12 weeks after finishing treatment. [12]

The pharmacokinetics (how the body absorbs, distributes and rids itself of a drug), safety and efficacy of sofosbuvir/velpatasvir, taken orally for 12 weeks, for the treatment of HCV genotypes 1, 2, 3, 4 or 6 infection was established in an open-label, multicenter clinical trial that included a total of 173 treatment-naïve and treatment-experienced pediatric subjects ages six years and older without cirrhosis or with mild cirrhosis. [7] No meaningful differences in pharmacokinetics were seen in pediatric subjects compared to adults. [7] The safety and efficacy results were comparable to those observed in adults. [7] In 102 subjects ages 12 through 17, 93% of subjects with genotype 1 and 100% of subjects with genotypes 2, 3, 4 and 6 had no detectable virus in the blood 12 weeks after finishing treatment, suggesting the subjects' infection was cured. [7] Among the 71 subjects ages 6 to 11 years with HCV genotypes 1, 2, 3 or 4, 93% with genotype 1, 91% with genotype 3 and 100% with genotypes 2 and genotype 4 had no virus detected in the blood 12 weeks after finishing treatment. [7]

The safety and efficacy of sofosbuvir/velpatasvir for treatment of HCV genotype 5 in pediatric subjects six years and older or weighing at least 37 pounds without cirrhosis or with mild cirrhosis are supported by sofosbuvir and velpatasvir exposures in adults and pediatric subjects with HCV genotype 1, 2, 3, 4 or 6 infection. [7] Similar data were used to support dosing recommendations for pediatric subjects with HCV genotype 1, 2, 3, 4, 5 or 6 infection who have severe cirrhosis. [7]

The safety and effectiveness of sofosbuvir/velpatasvir have not been established in people less than six years of age. [7]

The U.S. Food and Drug Administration (FDA) granted the application of sofosbuvir/velpatasvir priority review and granted the approval of Epclusa to Gilead Sciences, Inc. [12] [7]

Related Research Articles

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Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection period, people often have mild or no symptoms. Early symptoms can include fever, dark urine, abdominal pain, and yellow tinged skin. The virus persists in the liver, becoming chronic, in about 70% of those initially infected. Early on, chronic infection typically has no symptoms. Over many years however, it often leads to liver disease and occasionally cirrhosis. In some cases, those with cirrhosis will develop serious complications such as liver failure, liver cancer, or dilated blood vessels in the esophagus and stomach.

Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) co-infection is a multi-faceted, chronic condition that significantly impacts public health. According to the World Health Organization (WHO), 2 to 15% of those infected with HIV are also affected by HCV, increasing their risk of morbidity and mortality due to accelerated liver disease. The burden of co-infection is especially high in certain high-risk groups, such as intravenous drug users and men who have sex with men. These individuals who are HIV-positive are commonly co-infected with HCV due to shared routes of transmission including, but not limited to, exposure to HIV-positive blood, sexual intercourse, and passage of the Hepatitis C virus from mother to infant during childbirth.

<span class="mw-page-title-main">Boceprevir</span> Chemical compound

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<span class="mw-page-title-main">Sofosbuvir</span> Chemical compound

Sofosbuvir, sold under the brand name Sovaldi among others, is a medication used to treat hepatitis C. It is taken by mouth.

<span class="mw-page-title-main">Simeprevir</span> Chemical compound

Simeprevir, sold under the brand name Olysio among others, is a medication used in combination with other medications for the treatment of hepatitis C. It is specifically used for hepatitis C genotype 1 and 4. Medications it is used with include sofosbuvir or ribavirin and peginterferon-alfa. Cure rates are in 80s to 90s percent. It may be used in those who also have HIV/AIDS. It is taken by mouth once daily for typically 12 weeks.

<span class="mw-page-title-main">Ledipasvir</span> Hepatitis C drug

Ledipasvir is a drug for the treatment of hepatitis C that was developed by Gilead Sciences. After completing Phase III clinical trials, on February 10, 2014, Gilead filed for U.S. approval of a ledipasvir/sofosbuvir fixed-dose combination tablet for genotype 1 hepatitis C. The ledipasvir/sofosbuvir combination is a direct-acting antiviral agent that interferes with HCV replication and can be used to treat patients with genotypes 1a or 1b without PEG-interferon or ribavirin.

<span class="mw-page-title-main">Ombitasvir</span> Chemical compound

Ombitasvir is an antiviral drug for the treatment of hepatitis C virus (HCV) infection by AbbVie. In the United States, it is approved by the Food and Drug Administration for use in combination with paritaprevir, ritonavir and dasabuvir in the product Viekira Pak for the treatment of HCV genotype 1, and with paritaprevir and ritonavir in the product Technivie for the treatment of HCV genotype 4.

<span class="mw-page-title-main">Dasabuvir</span> Chemical compound

Dasabuvir, sold under the brand name Exviera, is an antiviral medication for the treatment of hepatitis C. It is often used together with the combination medication ombitasvir/paritaprevir/ritonavir specifically for hepatitis C virus (HCV) type 1. Ribavirin may also additionally be used. These combinations result in a cure in more than 90% of people. It is taken by mouth.

<span class="mw-page-title-main">Ledipasvir/sofosbuvir</span> Medication used to treat hepatitis C

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<span class="mw-page-title-main">Velpatasvir</span> Chemical compound

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References

  1. ↑ "Sofosbuvir / velpatasvir (Epclusa) Use During Pregnancy". Drugs.com. Archived from the original on 14 December 2017. Retrieved 13 December 2017.
  2. 1 2 3 4 5 6 7 "Sofosbuvir/Velpatasvir for the treatment of Hepatitis C" (PDF). WHO. Archived (PDF) from the original on 29 August 2021. Retrieved 29 June 2017.
  3. ↑ "Prescription medicines: registration of new chemical entities in Australia, 2016". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
  4. 1 2 3 4 "Epclusa 400 mg/100 mg film coated tablets. - Summary of Product Characteristics (SmPC)". (emc). 4 November 2019. Archived from the original on 2 March 2020. Retrieved 1 March 2020.
  5. 1 2 3 4 5 6 "Epclusa- velpatasvir and sofosbuvir tablet, film coated". DailyMed. 21 November 2019. Archived from the original on 16 March 2020. Retrieved 1 March 2020.
  6. 1 2 3 4 "Epclusa EPAR". European Medicines Agency (EMA). 27 February 2020. Archived from the original on 2 March 2020. Retrieved 1 March 2020.
  7. 1 2 3 4 5 6 7 8 9 10 11 12 "FDA Approves New Treatment for Pediatric Patients with Any Strain of Hepatitis C". U.S. Food and Drug Administration (FDA) (Press release). 19 March 2020. Archived from the original on 19 March 2020. Retrieved 19 March 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  8. 1 2 3 4 5 6 "Sofosbuvir and Velpatasvir". The American Society of Health-System Pharmacists. Archived from the original on 14 December 2017. Retrieved 8 December 2017.
  9. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  10. 1 2 Haberfeld, H, ed. (2016). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Epclusa 400 mg/100 mg Filmtabletten.
  11. ↑ US' Gilead faces competition from Bangladesh's Beacon pharma Archived 24 June 2017 at the Wayback Machine , The Economic Times
  12. 1 2 3 4 5 "FDA approves Epclusa for treatment of chronic Hepatitis C virus infection" (Press release). 28 July 2016. Archived from the original on 23 April 2019. Retrieved 28 July 2016.PD-icon.svg This article incorporates text from this source, which is in the public domain .
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